Toward the therapeutic editing of mutated RNA sequences.

If RNA editing could be rationally directed to mutated RNA sequences, genetic diseases caused by certain base substitutions could be treated. Here we use a synthetic complementary RNA oligonucleotide to direct the correction of a premature stop codon mutation in dystrophin RNA. The complementary RNA oligonucleotide was hybridized to a premature stop codon and the hybrid was treated with nuclear extracts containing the cellular enzyme double-stranded RNA adenosine deaminase. When the treated RNAs were translated in vitro, a dramatic increase in expression of a downstream luciferase coding region was observed. The cDNA sequence data are consistent with deamination of the adenosine in the UAG stop codon to inosine by double-stranded RNA adenosine deaminase. Injection of oligonucleotide-mRNA hybrids into Xenopus embryos also resulted in an increase in luciferase expression. These experiments demonstrate the principle of therapeutic RNA editing.

Apolipoprotein B mRNA-editing protein induces hepatocellular carcinoma and dysplasia in transgenic animals.

Apolipoprotein (apo-) B mRNA editing is the deamination of cytidine that creates a new termination codon and produces a truncated version of apo-B (apo-B48). The cytidine deaminase catalytic subunit [apo-B mRNA-editing enzyme catalytic polypeptide 1 (APOBEC-1)] of the multiprotein editing complex has been identified. We generated transgenic rabbits and mice expressing rabbit APOBEC-1 in their livers to determine whether hepatic expression would lower low density lipoprotein cholesterol concentrations. The apo-B mRNA from the livers of the transgenic mice and rabbit was extensively edited, and the transgenic animals had reduced concentrations of apo-B100 and low density lipoproteins compared with control animals. Unexpectedly, all of the transgenic mice and a transgenic rabbit had liver dysplasia, and many transgenic mice developed hepatocellular carcinomas. Many of the mouse livers were hyperplastic and filled with lipid. Other hepatic mRNAs with sequence motifs similar to apo-B mRNA were examined for this type of editing (i.e., cytidine deamination). One of these, tyrosine kinase, was edited in livers of transgenic mice but not of controls. This result demonstrates that other mRNAs can be edited by the overexpressed editing enzyme and suggests that aberrant editing of hepatic mRNAs involved in cell growth and regulation is the cause of the tumorigenesis. Finally, these findings compromise the potential use of APOBEC-1 for gene therapy to lower plasma levels of low density lipoproteins.

Evidence-based editing: factors influencing the number of citations in a national journal

Purpose: Citations received by papers published within a journal serve to increase its bibliometric impact. The objective of this paper was to assess the influence of publication language, article type, number of authors, and year of publication on the citations received by papers published in Gaceta Sanitaria, a Spanish-language journal of public health. Methods: The information sources were the journal website and the Web of Knowledge, of the Institute of Scientific Information. The period analyzed was from 2007 to 2010. We included original articles, brief original articles, and reviews published within that period. We extracted manually information regarding the variables analyzed and we also differentiated among total citations and self-citations. We constructed logistic regression models to analyze the probability of a Gaceta Sanitaria paper to be cited or not, taking into account the aforementioned independent variables. We also analyzed the probability of receiving citations from non-Spanish authors. Results: Two hundred forty papers fulfilled the inclusion criteria. The included papers received a total of 287 citations, which became 202 when excluding self-citations. The only variable influencing the probability of being cited was the publication year. After excluding never cited papers, time since publication and review papers had the highest probabilities of being cited. Papers in English and review articles had a higher probability of citation from non-Spanish authors. Conclusions: Publication language has no influence on the citations received by a national, non-English journal. Reviews in English have the highest probability of citation from abroad. Editors should decide how to manage this information when deciding policies to raise the bibliometric impact factor of their journals.

Zalpha-domains: At the intersection between RNA editing and innate immunity

The involvement of A to I RNA editing in antiviral responses was first indicated by the observation of genomic hyper-mutation for several RNA viruses in the course of persistent infections. However, in only a few cases an antiviral role was ever demonstrated and surprisingly, it turns out that ADARs - the RNA editing enzymes - may have a prominent pro-viral role through the modulation/down-regulation of the interferon response. A key role in this regulatory function of RNA editing is played by ADAR1, an interferon inducible RNA editing enzyme. A distinguishing feature of ADAR1, when compared with other ADARs, is the presence of a Z-DNA binding domain, Zalpha. Since the initial discovery of the specific and high affinity binding of Zalpha to CpG repeats in a left-handed helical conformation, other proteins, all related to the interferon response pathway, were shown to have similar domains throughout the vertebrate lineage. What is the biological function of this domain family remains unclear but a significant body of work provides pieces of a puzzle that points to an important role of Zalpha domains in the recognition of foreign nucleic acids in the cytoplasm by the innate immune system. Here we will provide an overview of our knowledge on ADAR1 function in interferon response with emphasis on Zalpha domains.

Outpatient prescription drugs : data collection and editing in the 1996 Medical Expenditure Panel Survey (HC-010A).

"June 2001."

LEFT: a language for editing and formating text,

"Supported in part by contract AT(11-1)-1018 with the U.S. Atomic Energy Commission and the Advanced Research Projects Agency."

Readings in documentary editing : a highly selective list compiled for the NHPRC Institute for the Editing of Historical Documents /

Shipping list no.: 95-0210-P.

Corpus Christianorum 1953-2003 : xenium natalicium : fifty years of scholarly editing /

Includes bibliographical references.

History of grazing; a circular offering suggestions on a technique for compiling data, writing, and editing material for a history of grazing.

Mimeographed.

Newspaper building, application of efficiency to editing, to mechanical production, to circulation and advertising, with cost finding methods, office forms and systems,

Mode of access: Internet.

A multiresolution terrain model for efficient visualization query processing

Multiresolution Triangular Mesh (MTM) models are widely used to improve the performance of large terrain visualization by replacing the original model with a simplified one. MTM models, which consist of both original and simplified data, are commonly stored in spatial database systems due to their size. The relatively slow access speed of disks makes data retrieval the bottleneck of such terrain visualization systems. Existing spatial access methods proposed to address this problem rely on main-memory MTM models, which leads to significant overhead during query processing. In this paper, we approach the problem from a new perspective and propose a novel MTM called direct mesh that is designed specifically for secondary storage. It supports available indexing methods natively and requires no modification to MTM structure. Experiment results, which are based on two real-world data sets, show an average performance improvement of 5-10 times over the existing methods.

Multiresolution spatial databases: Making web-based spatial advances faster

Spatial data has now been used extensively in the Web environment, providing online customized maps and supporting map-based applications. The full potential of Web-based spatial applications, however, has yet to be achieved due to performance issues related to the large sizes and high complexity of spatial data. In this paper, we introduce a multiresolution approach to spatial data management and query processing such that the database server can choose spatial data at the right resolution level for different Web applications. One highly desirable property of the proposed approach is that the server-side processing cost and network traffic can be reduced when the level of resolution required by applications are low. Another advantage is that our approach pushes complex multiresolution structures and algorithms into the spatial database engine. That is, the developer of spatial Web applications needs not to be concerned with such complexity. This paper explains the basic idea, technical feasibility and applications of multiresolution spatial databases.

Direct mesh: A multiresolution approach to terrain visualization

Terrain can be approximated by a triangular mesh consisting millions of 3D points. Multiresolution triangular mesh (MTM) structures are designed to support applications that use terrain data at variable levels of detail (LOD). Typically, an MTM adopts a tree structure where a parent node represents a lower-resolution approximation of its descendants. Given a region of interest (ROI) and a LOD, the process of retrieving the required terrain data from the database is to traverse the MTM tree from the root to reach all the nodes satisfying the ROI and LOD conditions. This process, while being commonly used for multiresolution terrain visualization, is inefficient as either a large number of sequential I/O operations or fetching a large amount of extraneous data is incurred. Various spatial indexes have been proposed in the past to address this problem, however level-by-level tree traversal remains a common practice in order to obtain topological information among the retrieved terrain data. A new MTM data structure called direct mesh is proposed. We demonstrate that with direct mesh the amount of data retrieval can be substantially reduced. Comparing with existing MTM indexing methods, a significant performance improvement has been observed for real-life terrain data.